1. Field of the Invention
This invention relates to advances in the field of facilitating contact with and adhesion to components of tooth and bone, and especially dentin.
Etching with acids, which is clinically successful in promoting adhesion of reconstructive composite and sealant resins to tooth enamel, see Buonocore, 34 J. Dent. Res. 849 (1955), is neither appropriate nor adequate to give bonding of these materials to dentin. Buonocore, M., The Acid Etch Technique 139 (1975). Dentin contains much more organic material and water than does enamel, and the concentration, arrangement, and morphology of the hydroxyapatite crystals are also different.
Adhesion of reconstructive synthetic resins to dentin presents difficulties not only because of the nature of dentin as a substrate, but also because of its biological vulnerability. Normal dentin contains a large number of dentinal tubules that extend from the enamel or cementum to the soft tissues of the pulp or root canal. Garberoglio et al., "Scanning Electron Microscope Investigation of Human Dentinal Tubules,"21 Archs. Oral Biol. 355-62 (1976). These tubules initially contain portions of vital odontoblasts, the cytoplasm of which extend a fraction of a millimeter peripherally from the pulp. The central and outermost portions of the tubules may contain only fluid or what appears in transmission electron micrographs to be a finely dispersed granular material. Whatever the nature and extent of the odontoblastic processes, there is evidence to support the contention that the health of odontoblasts requires that osmotic and hydrostatic influences on the tubular contents be maintained within certain limits. See Thomas, "The Extent of the Odontoblast Process in Human Dentin," 58 J. Dent. Res. 2207-18 (1979), Brannstrom et al., "The Dentinal Tubules and the Odontoblast Processes," 30 Acta Odont. Scand. 291-311 (1972); Johnson et al., "Pulp Irritation Due to the Phosphoric Acid Component of Silicate Cement," 29 Oral Surg. 447-54 (1970).
Desiccation of dentin probably destroys local odontoblasts. An air stream can remove water from pores smaller than a certain critical diameter in enamel, and this same principle applies to dentinal tubules provided that the surface tension is not lowered too much by surface-active solutes. Asmussen et al., "The Stability of Water in the Pores of Acid Etched Human Enamel," 36 Acta Odont. Scand. 43-45 (1978). This critical diameter is about 1.4 .mu.m for clean water in hydrophilic capillaries. The critical diameter is smaller if the water contains solutes (proteinaceous material, saliva, etc.) that lower the surface tension. The functional diameters of dentinal tubules can be smaller than this critical size, especially if they contain plugs of smeared surface material or other solids.
The vitality of these odontoblasts, and the pulpal soft tissues with which they associate, should be maintained throughout any procedures designed to restore hard-tooth tissues with adhesive materials. The health of these cells, as indicated, requires the maintenance of their environmental conditions within certain limits, including temperature, pH, osmotic pressure, the absence of toxic solutes, and other factors.
With regard to maintenance of osmotic pressure, odontoblastic cell membranes are believed to have some semipermeability. That is, they can be penetrated readily by water molecules but are relatively impermeable to (or have much lower transport rates for) larger solute molecules and hydrated ions. The present invention is designed to facilitate contacting with and adhesion to the dentinal surface while protecting that surface by neither abstracting water from nor giving up water to the dentin, relative to the normal homeostatic condition of the dentinal and pulpal tissues.
As presently suggested in the literature, the preparation of cut dentin for application of an adhering resin or composite material involves several steps.
Cut dentin starts out with a disturbed or "smeared" surface layer, and dentin that is uncovered by cervical erosion may be covered by a hydrated organic film of salivary pellicle.
These weak surface layers can be substantially removed by a brief exposure (typically 30 seconds; 5 to 120 seconds have been used) to a solution of buffered or unbuffered acids which is isotonic, that is, isosmotic with tissue, having pK.sub.a values between 3.8 and 2.5 and pH values of about 2.5.+-.0.6. Such acids of intermediate strength, for example formic acid, have given no perceptible evidence of pulp irritation in preliminary studies with animals. The pH of such "cleanser" solutions depends upon the pK.sub.a of the acids used and can, therefore, be adjusted independently while maintaining the desired osmotic pressure, which is a colligative property. The effects of various acids have been described. Bowen, 28(2) Int'l Dent. J. 97 (1978). See also Bowen, U.S. Pat. No. 4,251,565 and Bowen, Ser. No. 200,989, filed Oct. 27, 1980.
The dentin surface exposed by this acidic cleansing can be provided with improved cationic bonding sites by the brief application of certain metallic salts (such as ferric chloride), called "mordants," in isotonic concentrations. Bowen, R., "Adhesive Bonding of Various Materials to Hard Tooth Tissues VII. Metal Salts as Mordants for Coupling Agents," in Moskowitz, H., et al. (eds.), Dental Adhesive Materials 205 (1974); Bowen, 59 J. Dent. Res. 809 (1980). See also Bowen, Ser. No. 10,803, filed Feb. 9, 1979, and Bowen, Ser. No. 200,989, filed Oct. 27, 1980. In primates, pulp responses to this treatment also look encouraging.
In both the acid cleaning and mordant application procedures described above, the contents of the dentinal tubules are exposed to aqueous solutions that are isotonic, facilitating maintenance of normal osmotic and hydrostatic pressures.
The next step is the application of adhesion-promoting surface-active comonomers, see Bowen, U.S. Pat. No. 3,200,142; Bowen, 44 J. Dent. Res. 1369 (1965), which can bond via chelating groups to the surface-held cations of the substrate and mordant, see Misra and Bowen, 61 J. Coll. Interface Sci. 14 (1977), and can also copolymerize with the restorative dental resin applied subsequently. Bowen, "Properties of a Silica-Reinforced Polymer for Dental Restorations," 66 JADA 57-64 (1963); Bowen, U.S. Pat. No. 3,179,623. N-(2-hydroxy-3-methacryloxypropyl)-N-phenylglycine (NPG-GMA) and polyfunctional surface-active comonomers (PolySACs) are examples of such adhesion-promoting surface-active comonomers. Bowen, 44 J. Dent. Res. 895-911 (1965); Bowen, 58 J. Dent. Res. 1101-07 (1979). See also Bowen, U.S. Pat. No. 4,251,565 and Bowen, Ser. No. 200,989, filed Oct. 27, 1980.
Until now, these comonomers have been applied to the dentin as solutions in acetone or alcohol because they were not sufficiently soluble in monomers such as BIS-GMA and its formulations. Bowen, 66 JADA 57 (1963); Bowen, U.S. Pat. No. 3,066,112. However, the application of acetone or alcohol to the dentin would be expected to have a desiccating effect analogous to the application of a hypertonic solution, some of which have been shown to cause pain or otherwise insult the pulpal tissues.
2. Description of the Prior Art
U.S. Pat. No. 3,471,927 to Eisenberg teaches the application of, e.g., 20% benzyl alcohol plus 80% isopropanol as a liner in a prepared dental cavity. This mixture does not prevent dehydration of the tooth. The patentee apparently misinterprets the appearance of the treated tooth surface, which is coated by residual benzyl alcohol and does not appear dessicated, as evidence that the surface has not been dehydrated. For is the aromatic alcohol/aliphatic alcohol mixture a mixture of ethylenically unsaturated monomers.
U.S. Pat. No. 2,656,277 to Knappwost teaches the preparation and use of a kind of cement consisting of casein plus calcium oxide and calcium hydroxide, with trace amounts of sodium chloride, potassium chloride, and calcium chloride, which, when mixed with water, will be useful as an "underfilling material for tooth fillings". This cementitious material is not stated to be isotonic, nor is there any evidence given that this property was measured or controlled. The patentee refers to "isotonic blood salt solutions" only in naming the trace salts that are added to his formulation. His cement, as applied to the tooth, is not necessarily isotonic just because the dry powdered casein, calcium oxide, and calcium hydroxide are mixed with an aqueous solution containing chlorides of sodium, potassium, calcium, and magnesium in relative percentages substantially corresponding to hemoisotonic saline fluid. Equally important, it is not an ethylenically unsaturated monomer formulation and does not teach any way in which such a formulation could be made isotonic.
U.S. Pat. No. 4,148,988 to Masuhara et al. teaches a "curable composition" that contains acrylic or methacrylic monomers together with a specific aromatic dibasic acid having an ethylenically unsaturated group, such as 4-methacryloxyethyltrimellitate or its anhydride, related compounds, and mixtures of these. Curable compositions containing these compounds are claimed as a dental adhesive, but there is no teaching or claim of isotonicity or means of obtaining such compositions isotonic with normal physiological saline. One of the principal compounds claimed, the anhydride form of the coupling agent, would be incompatible with water as a composition because it would be hydrolyzed in the presence of water, and for a monomeric composition to be isotonic, it must contain some water.
U.S. Pat. No. 4,102,856 to Lee claims an alicyclic dimethacrylate as a novel component in dental restorative compositions, but teaches no way of making these dimethacrylates isotonic. U.S. Pat. Nos. 3,959,212; 4,150,012; 4,080,212 and 3,539,526 are drawn from related subject matter areas but are less pertinent.
The preparation of ethylenically unsaturated monomer formulations which are substantially isotonic with normal physiological saline solution, and especially their use as vehicles for the application of surface-active comonomers to a dentin surface, have not been described or suggested in any of the prior art. As a consequence, in the process of preparing for application of restorative resins in reconstructive dentistry, injury to dentinal and pulpal tissues has continued. It is with this background that the present invention must be viewed.